beta-Actin facilitates etoposide-induced p53 nuclear import
beta-Actin facilitates etoposide-induced p53 nuclear import
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β-肌动蛋白促进依托泊苷诱导的 p53 核输入
DOI：
10.1007/s12038-020-0004-2
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发表时间：
2020
影响因子：
2.9
通讯作者：
Ni Xiuzhen
中科院分区：
文献类型：
--
作者：
Qi Wenjing;Li Jinjiao;Pei Xiaohua;Ke Yueshuang;Bu Qingpan;Ni Xiuzhen
作为一种肿瘤抑制因子，P53在真核生物中保持了基因组的完整性。然而，关于P53在细胞质和细胞核之间穿梭的证据有限。以往的研究表明，β-肌动蛋白聚合通过与P53的相互作用负向调节P53的核输入。在本研究中，我们发现DNA损伤诱导β-肌动蛋白和P53在细胞核内积聚。β-肌动蛋白基因敲除损伤了P53的核转运。此外，β-肌动蛋白可与P53蛋白相互作用，P53蛋白在基因毒性应激反应中增强。此外，P53的N端缺失突变体显示与β-肌动蛋白的关联水平降低。我们进一步发现P53的Ser15、Thr18和Ser20在β-肌动蛋白：P53的相互作用中起关键作用，一旦突变为丙氨酸就会取消这种结合。综上所述，本研究揭示了β-肌动蛋白通过蛋白质-蛋白质相互作用调节P53的核输入。
As a tumor suppressor, p53 preserves genomic integrity in eukaryotes. However, limited evidence is available for the p53 shuttling between the cytoplasm and nucleus. Previous studies have shown that β-actin polymerization negatively regulates p53 nuclear import through its interaction with p53. In this study, we found that DNA damage induces both β-actin and p53 accumulation in the nucleus. β-actin knockdown impaired the nuclear transport of p53. Additionally, β-actin could interact with p53 which was enhanced in response to genotoxic stress. Furthermore, N terminal deletion mutants of p53 shows reduced levels of association with β-actin. We further identified Ser15, Thr18 and Ser20 of p53 are critical to the β-actin: p53 interaction, which upon mutation into alanine abrogates the binding. Taken together, this study reveals that β-actin regulates the nuclear import of p53 through protein–protein interaction.